Biomarkers for disease exist in a variety of forms such as numerical or structural chromosome aberrations, epigenetic factors or altered gene expression, abnormal levels of blood constituents or post-translational modifications. Often accurate diagnosis and prediction of response to therapy cannot rely on a single biomarker, but a combination of several, potentially very different types of markers. This multidisciplinary bioengineering project targets the development of a versatile, inexpensive technology platform termed 'disposable microfluidic chip' (dMFC). To support diagnostic efforts in assisted human reproduction and cancer research and therapy, this team of experienced investigators seeks to develop a dMFC capable of immobilizing individual cells in defined positions (Aim 1), interrogating multiple genetic loci for sensitive detection of numerical and structural chromosome aberrations in clinical samples (Aims 2-3) as well as the semi- quantitative analysis of gene transcripts or tumor-specific microRNAs (Aim 4). While this R21 project will investigate the feasibility of measuring multiple potential disease biomarkers including translocations, gene amplifications and expression of up to three tumor-specific microRNAs in small numbers of thyroid and breast cancer cells, the chip design can easily be modified to suit different applications such as noninvasive gene expression profiling in assisted human reproduction (ART) to predict oocyte competence and embryo survival. Thus, the successful completion of this feasibility study will equip us with a versatile prototype dMFC to develop more clinically oriented protocols in subsequent studies. PUBLIC HEALTH RELEVANCE: For accurate diagnosis, many situations require the assessment of not just one, but a combination of several different types of disease biomarkers. This multidisciplinary bioengineering project seeks to develop an inexpensive, versatile technology platform to detect and quantitate multiple biomarkers such as a combination of chromosomal alterations and aberrant gene expression in clinical samples.